Over the last decade, sales and adverse events due to opioid pain relievers (OPRs) in the US have quadrupled. The increasing use and abuse of OPRs impacts a wide range of the population, including pregnant women. Concomitant with increased in utero opioid exposures, there has been a dramatic increase in the incidence of neonatal abstinence syndrome (NAS), such that in the US, one infant is born every hour with signs of drug withdrawal from opioids. By 2009, more than 13,500 infants were born with NAS accounting for an estimated $720 million in healthcare expenditures nationwide. The state of Tennessee ranks second in the nation in number of prescriptions written for OPRs and rates of NAS have grown three times faster than the national average. Despite the rapid increase in NAS, underlying causes are poorly understood, resulting in inefficient use of healthcare utilization for all opioid-exposed infants. There is a critical need for research focused on understanding factors associated with developing NAS, including poly-substance abuse, co- prescribing of psychotropic medications and OPR prescription patterns. This research will inform efforts aimed at primary prevention of the NAS through modifying maternal and prescriber behaviors and more efficient use of healthcare resources through limiting unnecessary hospital observation of opioid-exposed infants who will not develop NAS. This project aims to: 1) determine predictors of NAS using vital statistics, administrative data, outpatient pharmacy data, statewide medical record review and drug screen data in a large population of infants in the Tennessee Medicaid Program, 2) determine if antenatal opioid prescribing patterns are associated with NAS and 3) develop a risk assessment tool for NAS. This study includes a rich array of data from the Tennessee Medicaid program comprising vital statistics, outpatient pharmacy data, hospital administrative data and statewide medical record review. In total, data will be obtained from more than 100,000 pregnant women and more than 1,000 infants diagnosed with NAS. The result of this series of projects will fill an existing gap i the literature on drug abuse, addiction and NAS that will be rapidly disseminated to inform clinicians and policymakers. The overarching objective of this mentored career development experience is for the candidate to emerge as an independent clinical investigator leading a multidisciplinary research program to improve care and outcomes for substance-exposed infants. To accomplish this goal, the candidate will augment his prior research training with advanced coursework and practical skills development in predictive modeling, pharmaco-epidemiology, leadership training and practical experiences focused on substance dependency treatment in pregnancy and maternal and infant public health systems. Throughout the award period, the candidate will work closely with a multidisciplinary team of mentors and advisors-including experts in pediatrics, obstetrics and gynecology, biostatistics, psychiatry, neonatology, critical care medicine, public health, and epidemiology-to carry out his stated career objectives and specific aims.